Experiments outlined in this proposal are designed to determine macrophage cytotoxicity and to elucidate some of the mechanisms of macrophage-mediated destruction of melanoma cells. Initially, the specificity of cytotoxicity of macrophages for tumor targets will be quantitated by the 51Cr-release method; cytostasis will be measured by the inhibition of 3H-thymidine incorporation. Next, the role of anti-melanoma antibody in the mediation of cytotoxicity will be investigated by using: a) cytophilic antibody; b) monoclonal anti-melanoma antibody, and c) circulating antibody from tumor-bearing mice. The proposed experiments are designed to resolve whether: a) this antibody is bound to the tumor cell or macrophage surface; b) cytophilic antibody enhances cytotoxicity; and c) blocking tumor surface antigens decreases cytotoxicity. Finally, to assess some of the steps in the generation of macrophages with tumor-killing potential, the cytological and functional capabilities of macrophage subpopulation in long-term culture will be determined by growth and characterization in semisolid medium.